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DOI10.1073/pnas.2018345118
The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles
Xi G.; An L.; Wang W.; Hao J.; Yang Q.; Ma L.; Lu J.; Wang Y.; Wang W.; Zhao W.; Liu J.; Yang M.; Wang X.; Zhang Z.; Zhang C.; Chu M.; Yue Y.; Yao F.; Zhang M.; Tian J.
发表日期2021
ISSN0027-8424
卷号118期号:22
英文摘要C-natriuretic peptide (CNP) and its receptor guanylyl cyclase, natriuretic peptide receptor 2 (NPR2), are key regulators of cyclic guanosine monophosphate (cGMP) homeostasis. The CNP-NPR2-cGMP signaling cascade plays an important role in the progression of oocyte meiosis, which is essential for fertility in female mammals. In preovulatory ovarian follicles, the luteinizing hormone (LH)-induced decrease in CNP and its encoding messenger RNA (mRNA) natriuretic peptide precursor C (Nppc) are a prerequisite for oocyte meiotic resumption. However, it has never been determined how LH decreases CNP/Nppc. In the present study, we identified that tristetraprolin (TTP), also known as zinc finger protein 36 (ZFP36), a ubiquitously expressed mRNA-destabilizing protein, is the critical mechanism that underlies the LH-induced decrease in Nppc mRNA. Zfp36 mRNA was transiently up-regulated in mural granulosa cells (MGCs) in response to the LH surge. Loss- and gain-of-function analyses indicated that TTP is required for Nppc mRNA degradation in preovulatory MGCs by targeting the rare noncanonical AU-rich element harbored in the Nppc 3' UTR. Moreover, MGC-specific knockout of Zfp36, as well as lentivirus-mediated knockdown in vivo, impaired the LH/hCG-induced Nppc mRNA decline and oocyte meiotic resumption. Furthermore, we found that LH/hCG activates Zfp36/ TTP expression through the EGFR-ERK1/2-dependent pathway. Our findings reveal a functional role of TTP-induced mRNA degradation, a global posttranscriptional regulation mechanism, in orchestrating the progression of oocyte meiosis. We also provided a mechanism for understanding CNP-dependent cGMP homeostasis in diverse cellular processes. © 2021 National Academy of Sciences. All rights reserved.
英文关键词CNP/Nppc; MRNA degradation; Mural granulosa cells; Oocyte meiosis; TTP/Zfp36
语种英语
scopus关键词chorionic gonadotropin; cyclic GMP; epidermal growth factor receptor; lentivirus vector; luteinizing hormone; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; tristetraprolin; messenger RNA; natriuretic peptide type C; tristetraprolin; Zfp36 protein, mouse; 3' untranslated region; animal cell; animal experiment; animal model; animal tissue; Article; AU rich element; cell function; controlled study; female; gene; gene expression regulation; gene knockout; granulosa cell; homeostasis; in vivo study; luteinizing hormone release; mammal; meiosis; mouse; nonhuman; Nppc gene; oocyte; ovary follicle; preovulatory follicle; protein function; RNA degradation; signal transduction; transcription regulation; upregulation; Zfp36 gene; animal; biosynthesis; genetics; Institute for Cancer Research mouse; metabolism; ovary follicle; ovulation; RNA stability; Animals; Female; Meiosis; Mice; Mice, Inbred ICR; Natriuretic Peptide, C-Type; Ovarian Follicle; Ovulation; RNA Stability; RNA, Messenger; Tristetraprolin
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/251164
作者单位Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
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Xi G.,An L.,Wang W.,et al. The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles[J],2021,118(22).
APA Xi G..,An L..,Wang W..,Hao J..,Yang Q..,...&Tian J..(2021).The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles.Proceedings of the National Academy of Sciences of the United States of America,118(22).
MLA Xi G.,et al."The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles".Proceedings of the National Academy of Sciences of the United States of America 118.22(2021).
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